Reciprocal organ interactions during heart failure: a position paper from the ESC Working Group on Myocardial Function

Abstract

Heart failure-either with reduced or preserved ejection fraction (HFrEF/HFpEF)-is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs.

Keywords: Liver; Adipose tissue; Brain; Heart failure; Intestine; Kidney; Lung; Multi-organ clinical syndrome; Non-coding RNAs.

Figure 1

Diagram of postulated organ crosstalk in heart disease—namely between the heart, kidneys, brain, lung, skeletal muscle, intestine, liver, adipose tissue, gonads, and the immune system. Details are elaborated in the respective subsections. RAAS, renin–angiotensin–aldosterone system; BNP, natriuretic brain peptide; AVP, argininge vasopressin; DAMP, danger associated molecular patterns; PRR, pattern recognition receptors.

Figure 2

Display of the hypothesized interaction between the failing heart and the intestine. TMAO, trimethylamine N-oxide.

Figure 3

Obesity-induces adipose tissue dysfunction (upper panel). The cardiac consequences of dysfunctional visceral, subcutaneous, epicardial, intramyocardial, and perivascular adipose tissue are depicted in the lower panel. Of note, certain cardiovascular actions are shared by distinct fat pads. ADRF, adipocyte-derived relaxing factors; ADCF, adipocyte-derived contracting factors.